Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment to the claims filed after non-final office action on June 22, 2026 is acknowledged. Claims 35-36, 54-55, 59 were amended, claims 1-34, 38, 41-53, 60-61 were canceled, claims 64-66 were newly added and claims 35-37, 39-40, 54-59, 62-66 are pending in the instant application.
Claims 35-37, 39-40, 54-59, 62-66 are examined on the merits of this office action
Withdrawn Rejections/Objections
The rejection of Claims 35-41, 55-63 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement is withdrawn in view of amendment of the claims filed June 22, 2026. Please note that claim 54 is still rejected due to amendment.
The rejection of Claim(s) 59 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed June 22, 2026.
The rejection of claims 35-37, 40 and 54-59, 62-66 on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. 11628222 in view of Brezksi (US20190127444) is withdrawn in view of amendment of the claims June 22, 2026 to remove overlapping sequences.
Maintained/Revised Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 54 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for delivery of siRNA molecules using CD71 binding FN3 domains and for modulation of gene or RNA expression by such siRNA molecules, doesn’t enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with claim 54.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
Claim 54 depends from claim 35, which has been amended to recite delivery of an siRNA molecule coupled to a CD71 binding FN3 domain. Claim 54 further recites that the siRNA molecule can elicit one or more cytotoxic effects by modulating gene expression, RNA expression or levels, tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition, or HDAC inhibition. The specification provides support for CD71-binding FN3 domains conjugated to siRNA molecules and demonstrates modulation of RNA expression using FN3 siRNA conjugates. However, the scope of claim 54 is not limited to modulation of gene expression or RNA expression of levels. Rather, claim 54 further encompasses siRNA molecules that elicit cytotoxic effects by additional recited mechanisms, including tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition and HDAC inhibition.
The specification does not teach these additional mechanisms in the context of the claimed siRNA molecules. Instead, the specification distinguishes siRNA molecules from other therapeutic or cytotoxic agents associated with such mechanisms. For example, paragraph 0025 separately identifies an anti tubulin agent, a siRNA molecule, DNA minor groove binders, topoisomerase inhibitors, and vinca alkaloids as alternative agents of interest. Paragraphs 0164-0168 similarly describe therapeutic or cytotoxic agents generally and identify mechanisms including tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition and HDAC inhibition.
The specification further demonstrates that these teachings concern therapeutic or cytotoxic agents other than siRNA. For example, paragraphs 0171-0172 identify conventional cytotoxic agents including dolastatins….vinca alkaloid. Paragraph 0171 specifically describes interference with microtubule dynamics by dolastatins and auristatins and attachment of such a drug to the FN3 domain.
Accordingly, while the specification teaches the claimed FN3-siRNA conjugate and siRNA mediated modulation of gene or RNA expression, it does not provide teaching commensurate with the full scope of amended claim 54, which now attributes the additional recited cytotoxic mechanisms or effects to the siRNA molecule.
The State of the Prior Art and the predictability or unpredictability of the art
A person of ordinary skill in the art would have understood that siRNA molecules may mediate sequence specific modulation of target RNA and consequent gene expression. However, the specification does not establish that an siRNA molecule would predictably elicit each of the additional cytotoxic effects recited in claim 54, including tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelatin…etc..as recited in instant claim 54.
As discussed above, the specification associates a number of these mechanisms with other classes of therapeutic or cytotoxic agents. Thus, the disclosure does not provide a predictable relationship between the disclosed FN3-siRNA embodiments and the full range of cytotoxic mechanisms or effects encompassed by amended claim 54.
The Relative Skill of Those in the Art
A person of ordinary skill in the art would likely have training in molecular biology, protein engineering, RNAi and drug delivery systems. However, in the absence of sufficient guidance in the specification identifying appropriate siRNA targets and establishing their relationship to the additional cytotoxic mechanisms recited in claim 54, even a skilled person would be required to determine which siRNA targets and siRNA molecules, if any, would elicit the claimed effects.
Amount of Guidance/ the Presence or Absence of Working Examples
The specification provides guidance and working examples concerning conjugation of FN3 domains to siRNA molecules and demonstrates modulation of target RNA expression using FN3-siRNA conjugates. Thus, the specification provides enabling guidance for embodiments of claim 54 involving modulation of gene expression or RNA expression or levels. However, the specification does not provide working examples demonstrating that an FN3-conjugated siRNA molecule elicits cytotoxic effects by the additional mechanisms recited in claim 54, such as tubulin binding, DNA binding, etc….HDAC inhibition. Rather, the specifications teachings concerning a number of these mechanisms are provided in connection with other therapeutic or cytotoxic agents.
Nor does the specification provide sufficient guidance identifying siRNA sequences, target genes, selection criteria, or other teachings that would permit a person of ordinary skill in the art to practice these additional embodiments throughout the scope of claim 54 without further experimentation.
The Quantity of Experimentation Necessary
In view of the number and diversity of cytotoxic mechanisms or effects encompassed by claim 54, and the absence of sufficient guidance or working examples connecting the disclosed siRNA molecules to those additional mechanisms or effects, a person of ordinary skill in the art would be required to identify appropriate biological targets, design or select corresponding siRNA molecules, and determine experimentally whether silencing such targets produces the particular cytotoxic effect recited by the claims. Such experimentation would not merely involve routine optimization of embodiments taught by the specification, but would require determining which siRNA embodiments, if any, provide the additional claimed cytotoxic mechanisms or effects that the specification otherwise describes in connection with different therapeutic or cytotoxic agents.
Therefore, in view of the Wands factors, the claims require undue experimentation to use the full scope of the claimed invention.
Response to Applicant’s Arguments
Applicants argue that claim 35 has been narrowed to require delivery of siRNA molecule. Furthermore, Applicants argue that the Examiner has not established the required reasonable basis for questioning enablement. Applicants argue that the Examiner bears the initial burden of establishing a reasonable basis for questioning whether the disclosure enables the claimed invention. Applicant argues that the BBB rationale is allegedly unsupported by the cited art. Applicant argues that the sequence recited in claim 35 constitutes a finite list of FN3 domains that were experimentally screened and confirmed to bind CD71, citing Example 6 and Tables 2-3. Applicant further relies on examples demonstrating FN3-CD71 binding, conjugation of FN3 domains to siRNA, and siRNA-mediated gene knockdown in peripheral tissues, including skeletal muscle and heart.
Applicant’s arguments have been fully considered but not found persuasive. Claim 35 has been amended to limit the agent of interest to an siRNA molecule, and Applicant has established that the recited FN3 sequences were experimentally identified as CD71 binders. The specification further provides working examples of FN3-siRNA conjugates and siRNA mediated gene knockdown. Thus, the previous concerns regarding the breadth of the agents, FN3 sequences and BBB delivery are no longer commensurate with the presently claimed invention. Therefore, upon reconsideration of the amended claims, Applicant’s arguments, and the evidence of record, the rejection of claims 35-41 and 55-63 for lack of enablement is withdrawn. However, amended claim 54 remains rejected due to separate/new issues under 112(a) and 112(b), in particular the “siRNA molecule” and the cytotoxic mechanisms (see above and below rejections).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 35-37, 39-40, 54-59, 62-66 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 16, 18, 20-22, 24-32 of copending Application No. 18/863539(reference application) in view of Brezksi (US20190127444, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of delivering an agent of interest to a CD71 positive cell, the method comprising contacting the cell with the agent of interest coupled to an FN3 domain that binds to CD71, wherein the FN3 domain comprises an amino acid sequence of SEQ ID NO: 209, 1-7, 10, 12-208, 210-219, 221-272, 292-299, or 304-306” (claim 35). The instant application further claims wherein the agent of interest is siRNA molecule (claim 56-58); antisense molecule (claim 59); wherein the cell is a muscle cell (claim 40); a cell in the BBB (claim 41); agent of interest is DNA molecule (claim 61); a further half life extending moiety (Claims 62-63).
Co-pending application 18/863539 claims “A method of reducing glycogen levels in a subject in need thereof, the method comprising administering a composition comprising one or more FN3 domains conjugated to an siRNA molecule, wherein the siRNA molecule comprises a sense strand and an antisense strand, and wherein the one or more FN3 domains comprises an FN3 domain that binds CD71 and the siRNA molecule targets GYS 1” (claim 1). Co-pending application 18/863539 further claims wherein the FN3 domain that binds CD71 comprises an amino acid sequence that is at least 87% identical to, or is identical to, a sequence of SEQ ID NO: 509, 708, 710, 273, 288-291, 301-310,312-508, 510-572,or 592-599 (see claim 24) which SEQ ID NO:509 is instant SEQ ID NO:209 and 512 is identical to instant SEQ ID NO:212; delivery to a muscle cell (claim 32); administration to a subject would meet contacting the cell and would inherently contact a cell in the BBB. Thus, Co-pending application 18/863539 a method of using an FN3 domain of the instant claims coupled to a therapeutic, in particular siRNA and to the muscle thus meeting the limitations of the instant claims.
Co-pending application 18/863539 is silent to including a hall-life extending moiety administration including muscular.
However, Brezski teaches FN3 fusions comprising half-life extending moieties (see claim 1, paragraph 0013, paragraph 0093). It would have been obvious before the effective filing date of the claimed invention to conjugate or fuse a half-life extending moiety. One of ordinary skill in the art would have been motivated to do so because it would advantageous to increase the half life (prolong the activity of the therapeutic) in the method of Co-pending application 18/863539. Regarding claims 65-66, parenteral administration, including intramuscular, would have been obvious selection of a well-known route for administering therapeutic agents to the particular site of interest with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant notes that the '539 application was published on December 4, 2025, and has a priority date of May 6, 2022, which is later than the effective filing date of the instant application, March 28, 2022.
If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent.
Applicant’s arguments have been fully considered but not found persuasive. The provisional nonstatutory double patenting rejection is maintained because the claims of the instant applicant are not patentably distinct from the claims of the copending application. The relative filing dates do not, at this stage of prosecution, overcome the provisional double patenting rejection.
Claims 35-37, 39-40, 54-59, 62-66 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91, 98-130 of copending Application No. 19/039752(reference application) in view of Brezksi (US20190127444, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of delivering an agent of interest to a CD71 positive cell, the method comprising contacting the cell with the agent of interest coupled to an FN3 domain that binds to CD71, wherein the FN3 domain comprises an amino acid sequence of SEQ ID NO: 209, 1-7, 10, 12-208, 210-219, 221-272, 292-299, or 304-306” (claim 35). The instant application further claims wherein the agent of interest is siRNA molecule (claim 56-58); antisense molecule (claim 59); wherein the cell is a muscle cell (claim 40); a cell in the BBB (claim 41); agent of interest is DNA molecule (claim 61); a further half life extending moiety (Claims 62-63).
Co-pending application 19/039752 claims a method of treating a disease comprising administering FN3 coupled to siRNA (see claim 91). Co-pending application 19/039752 further claims wherein the cells over the BBB or muscle cell (claim 99); wherein the FN3 comprises SEQ ID Nos:519, 515 or 511 which are identical to instant SEQ ID Nos:219, 215 and 211 and SEQ ID NO:515 which is identical to instant SEQ IDNO:215; SEQ ID NO:509 which is instant SEQ ID NO:209 (Claim 117).
Co-pending application 19/039752 is silent to including a hall-life extending moiety.
However, Brezski teaches FN3 fusions comprising half-life extending moieties (see claim 1, paragraph 0013, paragraph 0093). It would have been obvious before the effective filing date of the claimed invention to conjugate or fuse a half-life extending moiety. One of ordinary skill in the art would have been motivated to do so because it would advantageous to increase the half life (prolong the activity of the therapeutic) in the method of Co-pending application 19/039752. Regarding claims 65-66, parenteral administration, including intramuscular, would have been obvious selection of a well-known route for administering therapeutic agents to the particular site of interest with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicants argue that “Because the instant application and the '752 application share the same effective filing date, Applicant respectfully asserts that the two-way test for obviousness-type double patenting should be applied. See M.P.E.P. § 804. Under the two-way test, the claims must be obvious in both directions, i.e., the instant claims over the reference claims and the reference claims over the instant claims. The claims of the '752 application are patentably distinct from the instant claims. The pending claims of the '752 application recite an siRNA molecule having specific nucleobase sequences selected from defined pairs. The Office has not demonstrated that the claims of the '752 application would have been obvious in view of the pending claims.
Accordingly, the instant claims and the '752 claims are patentably distinct, and the rejection should be withdrawn.
Applicant’s arguments have been fully considered but not found persuasive. Although Applicant argues that the two-way test applies and that the claims of the ‘752 application are patentably distinct because they recite particular siRNA nucleotide sequences, the claims remain patentably indistinct. The relied upon claims encompass the same CD71 binding FN3 domains and their use for delivery of siRNA to the same claimed cell types. The recitation of siRNA sequences does not render the claimed subject matter patentably distinct from the instant claims. Accordingly, the provisional nonstatutory double patenting rejection is maintained.
Claims 35-37, 39-40, 54-59, 62-66 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20, 22-23, 25-26 of copending Application No. 18/301036 (reference application) in view of Brezksi (US20190127444, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of delivering an agent of interest to a CD71 positive cell, the method comprising contacting the cell with the agent of interest coupled to an FN3 domain that binds to CD71, wherein the FN3 domain comprises an amino acid sequence of SEQ ID NO: 209, 1-7, 10, 12-208, 210-219, 221-272, 292-299, or 304-306” (claim 35). The instant application further claims wherein the agent of interest is siRNA molecule (claim 56-58); antisense molecule (claim 59); wherein the cell is a muscle cell (claim 40); a cell in the BBB (claim 41); agent of interest is DNA molecule (claim 61); a further half life extending moiety (Claims 62-63).
Co-pending application 18/301036 claims a method of treating a disease comprising administering FN3 coupled to siRNA (see claim 1). Co-pending application 18/301036 further claims wherein the FN3 comprises SEQ ID Nos:519, 515 or 511 which are identical to instant SEQ ID Nos:219, 215 and 211 and 509 which is instant SEQ ID NO:209 (se claims 12-15); SEQ ID NO:512 is instant SEQ ID NO: 212; administration to a subject would meet contacting the cell (see claim 1).
Co-pending application 18/301036 is silent to including a hall-life extending moiety and form of administration.
However, Brezski teaches FN3 fusions comprising half-life extending moieties (see claim 1, paragraph 0013, paragraph 0093). It would have been obvious before the effective filing date of the claimed invention to conjugate or fuse a half-life extending moiety. One of ordinary skill in the art would have been motivated to do so because it would advantageous to increase the half life (prolong the activity of the therapeutic) in the method of Co-pending application 18/301036.
Regarding claims 65-66, parenteral administration, including intramuscular, would have been obvious selection of a well-known route for administering therapeutic agents to the particular site of interest with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant notes that the '036 application was published on February 8, 2024, and has a priority date of April 14, 2022, which is later than the effective filing date of the instant application, March 28, 2022.
In view of the foregoing, Applicant respectfully requests that the rejection on the ground of provisional nonstatutory double patenting be withdrawn.
Applicant’s arguments have been fully considered but not found persuasive. The relative filing dates do not, by themselves, establish that the provisionally rejected claims are patentably distinct. As set forth above, the claims of the instant application and the reference application are not patentably distinct. Accordingly, the provisional nonstatutory double patenting rejection is maintained.
Claims 35-37, 39-40, 54-59, 62-66 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 10-21, 23-25 of copending Application No. 18/490450 (reference application) in view of Brezksi (US20190127444). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of delivering an agent of interest to a CD71 positive cell, the method comprising contacting the cell with the agent of interest coupled to an FN3 domain that binds to CD71, wherein the FN3 domain comprises an amino acid sequence of SEQ ID NO: 209, 1-7, 10, 12-208, 210-219, 221-272, 292-299, or 304-306” (claim 35). The instant application further claims wherein the agent of interest is siRNA molecule (claim 56-58); antisense molecule (claim 59); wherein the cell is a muscle cell (claim 40); a cell in the BBB (claim 41); agent of interest is DNA molecule (claim 61); a further half life extending moiety (Claims 62-63).
Co-pending application 18/490540 claims a method of treating a disease comprising administering FN3 coupled to siRNA (see claim 1). Co-pending application 18/490450 further claims wherein the FN3 comprises SEQ ID Nos:570 which is identical to instant SEQ ID NO:209 (see claim21); SEQ ID NO:276 which is identical to 215; administration to a subject would meet contacting the cell and would inherently contact a cell in the BBB.
Co-pending application 18/490540 is silent to including a hall-life extending moiety or route of administration.
However, Brezski teaches FN3 fusions comprising half-life extending moieties (see claim 1, paragraph 0013, paragraph 0093). It would have been obvious before the effective filing date of the claimed invention to conjugate or fuse a half-life extending moiety. One of ordinary skill in the art would have been motivated to do so because it would advantageous to increase the half life (prolong the activity of the therapeutic) in the method of Co-pending application 18/490540.
Regarding claims 65-66, parenteral administration, including intramuscular, would have been obvious selection of a well-known route for administering therapeutic agents to the particular site of interest with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant notes that the '450 application was published on May 30, 2024, and has a priority date of June 2, 2023, which is later than the effective filing date of the instant application, March 28, 2022.
In view of the foregoing, Applicant respectfully requests that the rejection on the ground of provisional nonstatutory double patenting be withdrawn.
Applicant’s arguments have been fully considered but not found persuasive. The relative filing dates do not, by themselves, establish that the provisionally rejected claims are patentably distinct. As set forth above, the claims of the instant application and the reference application are not patentably distinct. Accordingly, the provisional nonstatutory double patenting rejection is maintained.
New Rejections
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 35-37, 39-40, 54-59, 62-66 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 35 is rejected because the limitation “administering to the subject with the siRNA molecule coupled to an FN3 domain…” is unclear because the claim does not clearly identify what is being administering to the subject. Accordingly, the metes and bounds of the claimed method cannot be determined. Claims 36-37, 39-40, 54-59 and 62-66 are also rejected due to their dependence on claim 35 and not clarifying this point of confusion. A suggested amendment if applicants are wanting administering the conjugate would be -the method comprising administering to the subject
Claim 54 depends from claim 35 and recites, in part, “the siRNA molecule can elicit one or more cytotoxic effects by modulating gene expression, RNA expression or levels, tubulin binding, DNA binding, topoisomerase inhibition, DNA cross-linking, chelation, spliceosome inhibition, NAMPT inhibition, or HDAC inhibition”. It is unclear whether the claim requires the siRNA molecule itself to produce the recited cytotoxic effects through the listed mechanisms, or whether the claim encompasses downstream effects resulting from siRNA mediated modulation of gene or RNA expression. This raises ambiguity because the specification describes siRNA separately from other therapeutic or cytotoxic agents associated with several of the recited mechanisms. For example, paragraph 0025 separately identifies siRNA molecules, anti tubulin agents, DNA minor groove binders, and topoisomerase inhibitors, while paragraphs 0167-0176 describe various cytotoxic mechanisms and therapeutic agents or moieties. Thus, one of ordinary skill in the art would not know with reasonable certainty whether the recited mechanisms must be activities of the siRNA molecule itself or may instead constitute downstream consequences of siRNA-mediated gene or RNA modulation. Therefore the scope of claim 54 is indefinite.
Claim 65 is rejected because the limitation “administering to the via parenteral…” is unclear because the claim does not clearly identify who is being administered to. Accordingly, the metes and bounds of the claimed method cannot be determined. A suggested amendment would be -administered to the subject via…-
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 54 is rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement (new matter). The claim(s) contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time of the application was filed, had possession of the claimed invention.
Claim 54 has been amended to recite that “the siRNA molecule can elicit one or more cytotoxic effects by modulating gene expression, RNA expression or levels, tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition or HDAC inhibition”.
Lack of Ipsis Verbis Support
The specification is void of any literal support for siRNA molecules that can elicit cytotoxic effects by tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition or HDAC inhibition. Although the specification separately discloses siRNA molecules and the recited cytotoxic mechanisms, it does not disclose the particular combination now recited in amended claim 54. For example, paragraph 0025 identifies an anti tubulin agent, an siRNA molecule, DNA minor groove binders, topoisomerase inhibitors, and vinca alkaloids as separate agents of interest. Paragraphs 0167-0168 describe the recited cytotoxic mechanisms in connection with therapeutic agents generally, and paragraphs 0171-0176 further describe cytotoxic agents and chelating agents or moieties distinct from siRNA molecules. Thus, the amendment replacing the previously recited “agent of interest” with siRNA molecule results in the listed cytotoxic mechanisms being specifically attributed to the siRNA molecule. The specification as originally filed does not expressly describe this combination.
An ordinary-skilled artisan cannot clearly envisage siRNA molecules with the claimed cytotoxic mechanisms. Thus, such limitations recited in the present claims, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. §112. Applicant is required to cancel the new matter in the response to this Office Action. Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP §714.02, §2163.05-06 and §2173.05(i).
Lack of Implicit or Inherent Support
“While there is not in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure.” See MPEP 2163. Thus support can be furnished implicitly or inherently for a specifically claimed limitation. The specification expressly supports siRNA mediated modulation of gene or RNA expression. However, the disclosure does not establish that an siRNA molecule necessarily, or implicitly as part of the disclosed invention, elicits cytotoxic effects by tubulin binding, DNA binding, topoisomerase inhibition, DNA cross linking, chelation, spliceosome inhibition, NAMPT inhibition, or HDAC inhibition. Rather, as discussed above, the specification associated these mechanisms with therapeutic or cytotoxic agents generally and separately identifies siRNA as an agent of interest. Therefore, the specification does not provide sufficient express, implicit, or inherent written description support for the newly added limitation, and claim 54 fails to comply with the written description requirement.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERINNE R DABKOWSKI/ Primary Examiner, Art Unit 1654
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